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Background The early diagnosis of Alzheimer's disease (AD) in large-scale high-risk population is a major challenge. Blood-based biomarkers could enable widespread testing for AD. RNA-seq technology is becoming an effective method in investigating diagnostic biomarkers for diseases, but platforms exploring RNA-seq data in AD blood are lacking. Methods We collected the raw RNA-seq data in the blood of AD patients or AD mouse models, mild cognitive impairment (MCI) patients, and normal people or wild type mouse from the Gene Expression Omnibus (GEO) and Synapse databases. And the RNA-seq data was analyzed by the standard pipeline. We applied R-Shiny to develop the website of RAD-Blood (RNA-seq analysis of AD blood, http://www.bioinform.cn/RAD-Blood/) to present the plentiful analysis results. Results RAD-Blood was specifically designed to analyze existing blood RNA-seq data sets (mRNA-seq, miRNA-seq, and scRNA-seq) from patients and mouse models with AD pathology. The RAD-Blood provides differential expression, gene set enrichment, immune abundance and its correlation with gene expression, cell type annotation, T cell receptor, and cell communication analyses for RNA-seq data in AD/MCI/normal blood, with rich results forms and colorful figures. We used a case study to show the capacity of RAD-Blood in finding blood biomarkers in AD/MCI blood. By using RAD-Blood, we found 274 protein-coding genes whose mRNA expression was consistently up-regulated or down-regulated from normal to MCI to AD. Among the consistently down-regulated genes, four are the markers of the blood erythroid cell. Compared with normal people, the population of erythroid cells in AD patients decreased. Despite the reduction in cell count, interactions between blood erythroid cells with other cells increased dramatically, which is mainly mediated through the major histocompatibility complex I (MHC-I) signaling pathway. These findings have not been reported by existing studies, which suggests that RAD-Blood is a solution for finding potential novel signatures in the blood of AD and MCI. Conclusions RAD-Blood is a user-friendly web server for multi-level analysis and visualization of gene/miRNA expression and immune profile in AD blood, and allows broad utility in exploring potential AD blood biomarkers, testing hypotheses, guiding experiment design, and investigating the peripheral pathogenic mechanisms and proposing potential early diagnosis standard of AD.

Protein N-glycosylation plays critical roles in modulating placental function, but little is known about N-glycoproteins in the human placenta and modifications in preeclampsia (PE). Here, we show a large, site-specific N-glycoproteome profiling study of PE and normal placenta using quantitative N-glycoproteomics based on mass spectrometry. The study identified disease signatures of altered N-glycoproteins and N-glycosylation site occupancy in PE and provided a system-level view of human placental N-glycoproteins and in vivo N-glycosylation sites. The study led to the discovery of a roster of glycoproteins with aberrant N-glycosylation levels associated with PE, including CD34, ENPP1 (ectonucleotide pyrophosphatase/phosphodiesterase family member 1), insulin-like growth factor binding protein (IGFBP3), and HYOU1 (hypoxia up-regulated 1). An emerging phenomenon that N-glycosylation is involved in several PE pathways, including cell adhesion molecules, PI3K-Akt signaling, pyrimidine metabolism, and metabolic pathways was revealed by pathway analysis of PE-associated aberrant glycoproteins. After enzymolysis, the proteins in each group were enriched with N-glycosylated peptides by lectin, the glycochain was excised by peptide N-glycosidase F (PNGase F) in H218O, and the glycosylated sites were analyzed by LC-MS/MS to achieve large-scale qualitative and quantitative analysis of N-glycosylated proteins. Our findings highlight the role of N-glycosylation in the pathogenesis of PE and provide new molecular and system-level insights for understanding and treating this disease.

The disruption of epigenetic regulation is common in tumors; the abnormal expression of epigenetic factors leads to cancer occurrence and development. In this study, to investigate the potential function of histone methylation regulators in lung adenocarcinoma (LUAD), we performed differential expression analysis using RNA-seq data downloaded from The Cancer Genome Atlas (TCGA) database, and identified CBX2 and EZH2 as obviously upregulated histone methylation regulators. CBX2 knockdown significantly inhibited LUAD cell growth and metastasis in vitro and in vivo. The combined high expression of CBX2 and EZH2 was an indicator of poor prognosis in LUAD. The inhibition of both CBX2 and EZH2 exerted cooperative suppressive effects on the growth and metastasis of LUAD cells. Mechanistically, we revealed that CBX2 and EZH2 downregulated several PPAR signaling pathway genes and tumor suppressor genes through binding to their promoter cooperatively or separately. Furthermore, knockdown of CBX2 improved the therapeutic efficiency of EZH2 inhibitor on A549 cells. Our study reveals the cooperative oncogenic role of CBX2 and EZH2 in promoting LUAD progression, thereby providing potential targets for LUAD diagnosis and therapy., Graphical abstract, Two significantly upregulated histone methylation related genes, CBX2 and EZH2, suppress the transcription of several PPAR signaling pathway genes and tumor suppressor genes, showing a cooperative effect on suppressing lung adenocarcinomal development and revealing the potential clinical application of developing CBX2 inhibitors in combination with EZH2 inhibitors to treat LUAD.

Cancer initiation and progression are likely caused by the dysregulation of biological pathways. Gene set analysis (GSA) could improve the signal-to-noise ratio and identify potential biological insights on the gene set level. However, platforms exploring cancer multi-omics data using GSA methods are lacking. In this study, we upgraded our GSCALite to GSCA (gene set cancer analysis, http://bioinfo.life.hust.edu.cn/GSCA) for cancer GSA at genomic, pharmacogenomic and immunogenomic levels. In this improved GSCA, we integrated expression, mutation, drug sensitivity and clinical data from four public data sources for 33 cancer types. We introduced useful features to GSCA, including associations between immune infiltration with gene expression and genomic variations, and associations between gene set expression/mutation and clinical outcomes. GSCA has four main functional modules for cancer GSA to explore, analyze and visualize expression, genomic variations, tumor immune infiltration, drug sensitivity and their associations with clinical outcomes. We used case studies of three gene sets: (i) seven cell cycle genes, (ii) tumor suppressor genes of PI3K pathway and (iii) oncogenes of PI3K pathway to prove the advantage of GSCA over single gene analysis. We found novel associations of gene set expression and mutation with clinical outcomes in different cancer types on gene set level, while on single gene analysis level, they are not significant associations. In conclusion, GSCA is a user-friendly web server and a useful resource for conducting hypothesis tests by using GSA methods at genomic, pharmacogenomic and immunogenomic levels.

Background: Cytogenetically normal acute myeloid leukemia (CN-AML) is a large proportion of AMLs with diverse prognostic outcomes. Identifying membrane protein genes as prognostic factors to stratify CN-AML patients will be critical to improve their outcomes. Purpose: This study aims to identify prognostic factors to stratify CN-AML patients to choose better treatments and improve their outcomes. Methods: CN-AML data were from TCGA cohort (n = 79) and four GEO datasets. We identified independent prognostic genes by Cox regression and Kaplan-Meier methods, and constructed linear regression model using LASSO algorithm. The prediction error curve was calculated using R package "pec". Results: Based on independent prognostic membrane genes, we constructed a regression model for CN-AML prognosis prediction: score = (0.0492 * CD52) - (0.0018 * CD96) + (0.0131 * EMP1) + (0.2058 * TSPAN2) + (0.0234 * STAB1) - (0.3658 * MBTPS1), which was named as MPG6 (6-Membrane Protein Gene) score. Tested in multiple CN-AML datasets, consistent results showed that CN-AML patients with high MPG6 score had poor survival, higher WBC count and shorter EFS. Comparing with other reported scoring models, the benchmark result of MPG6 achieved better association with survival in multiple cohorts. Moreover, by combining with other clinical indicators in CN-AML, MPG6 could improve the performance of survival prediction and serve as a robust prognostic factor. Conclusions: We identified the MPG6 score as a stable indicator with great potential for clinical application in risk stratification and outcome prediction in CN-AML.

Background: Despite the improved access to health services in China, inadequate diagnosis and management of dementia are common issues, especially in rural regions. Objective: The Hubei Memory & Aging Cohort Study was designed as a prospective study in Central China to determine the prevalence, incidence, and risk factors for dementia and mild cognitive impairment (MCI) among urban and rural older adults. Methods: From 2018–2020, participants aged ≥65 years were screened, and data regarding their life behaviors, families, socio-economic status, physical and mental health, social and psychological factors, and cognition were collected. Diagnoses of MCI and dementia were made via consensus diagnosis using the Diagnostic and Statistical Manual of Mental Disorders fourth edition criteria. Results: Of 8,221 individuals who completed their baseline clinical evaluation, 4,449 (54.1%) were women and 3,164 (38.4%) were from remote rural areas (average age: 71.96 years; mean education period: 7.58 years). At baseline, 25.98%(95%confidence interval [CI]: 24.99–26.96) and 7.24%(95%CI: 6.68–7.80) of the participants were diagnosed with MCI and dementia, respectively. Prevalence showed a strong relationship with age. The substantial disparities between rural and urban regions in MCI and dementia prevalence and multiple dementia-related risk factors were revealed. Especially for dementia, the prevalence rate in rural areas was 2.65 times higher than that in urban regions. Conclusion: Our results suggested that public health interventions are urgently needed to achieve equitable diagnosis and management for people living with dementia in the communities across urban and rural areas.

Background: Some studies have demonstrated an association between low and high body mass index (BMI) and an increased risk of dementia. However, only a few of these studies were performed in rural areas. Objective: This cross–sectional study investigated the associations between BMI and cognitive impairment among community–dwelling older adults from rural and urban areas. Methods: 8,221 older persons enrolled in the Hubei Memory & Ageing Cohort Study (HMACS) were recruited. Sociodemographic and lifestyle data, comorbidities, physical measurements, and clinical diagnoses of cognitive impairment were analyzed. Logistic regression was performed to assess the associations of BMI categories with cognitive impairment. A series of sensitivity analyses were conducted to test whether reverse causality could influence our results. Results: Being underweight in the rural–dwelling participants increased the risk of cognitive impairment. Being overweight was a protective factor in rural–dwelling participants aged 65–69 years and 75–79 years, whereas being underweight was significantly associated with cognitive impairment (OR, 1.37; 95% CI: 1.03–1.83; p

Background The prevalence of dementia in China, particularly in rural areas, is consistently increasing; however, research on population-attributable fractions (PAFs) of risk factors for dementia is scarce. Methods We conducted a cross-sectional survey, namely, the China Multicentre Dementia Survey (CMDS) in selected rural and urban areas from 2018 to 2020. We performed face-to-face interviews and neuropsychological and clinical assessments to reach a consensus on dementia diagnosis. Prevalence and weighted PAFs of eight modifiable risk factors (six classical: less childhood education, hearing impairment, depression, physical inactivity, diabetes, and social isolation, and two novels: olfactory decline and being unmarried) for all-cause dementia were estimated. Results Overall, CMDS included 17,589 respondents aged ≥ 65 years, 55.6% of whom were rural residents. The age- and sex-adjusted prevalence for all-cause dementia was 9.11% (95% CI 8.96-9.26), 5.19% (5.07-5.31), and 11.98% (11.8-12.15) in the whole, urban, and rural areas of China, respectively. Further, the overall weighted PAFs of the eight potentially modifiable risk factors were 53.72% (95% CI 52.73-54.71), 50.64% (49.4-51.89), and 56.54% (55.62-57.46) in the whole, urban, and rural areas of China, respectively. The eight risk factors' prevalence differed between rural and urban areas. Lower childhood education (PAF: 13.92%) and physical inactivity (16.99%) were primary risk factors in rural and urban areas, respectively. Conclusions The substantial urban-rural disparities in the prevalence of dementia and its risk factors exist, suggesting the requirement of resident-specific dementia-prevention strategies.

Background Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide, but its regulatory mechanism remains unclear. Although many TFs and miRNAs are reported to be important in HCC, their co-regulation and FFL modules in HCC development are needed to be investigated. Methods The feed-forward loop (FFL) regulatory module was identified by analyzing the miRNA and transcription factor co-regulatory network for differentially expressed genes between tumors and matched adjacent tissue samples. Gene expression and regulatory role of HCC development by key FFL in vitro and in vivo were validated by qPCR, Western blotting, cell proliferation assay, migration and invasion assay and experiments in nude mice with hepatoma xenografts. Results Here, by bioinformatics analysis, we identified FFL regulatory module miR-9-5p/FOXO1/CPEB3 may play critical roles in HCC progression. Gain- and loss-of-function studies demonstrated that miR-9-5p promote hepatocarcinogenesis, while FOXO1 and CPEB3 inhibit hepatocarcinoma growth. Furthermore, CPEB3 was firstly identified as a direct downstream target of miR-9-5p and FOXO1 by luciferase reporter assay and ChIP-Seq data, which was negatively regulated by miR-9-5p and activated by FOXO1. Following, the miR-9-5p/FOXO1/CPEB3 FFL was associated with poor prognosis and promoted cell growth and tumorigenesis of HCC in both in vitro and in vivo experiments. Conclusion Our study newly identified the existence of miR-9-5p/FOXO1/CPEB3 FFL and revealed its regulatory role in HCC progression, which may represent a new potential therapeutic target for cancer treatment.

By simulating constant climate environment, the internal temperature response tests of concrete were carried out considering the influences of different crack width and depth conditions. Besides, t...

Studies have shown that contact with nature plays a crucial role in the amelioration of human health. Forest therapy has recently received widespread attention as a novel and subsidiary treatment approach for stress recovery and health promotion. However, there is a lack of ample research on the comprehensive evaluation of the forest healthcare benefits. Moreover, it is not entirely clear what kind of forest types and seasons are suitable for forest therapy activities and how healthcare forests should be constructed and managed. From September 2019 to January 2020 and May to August 2020., five forest types of Phyllostachys edulis forest, subtropical evergreen broad-leaved forest, Liquidambar formosana forest, Cunninghamia lanceolata forest, coniferous and broad-leaved mixed forest and a forestless control group in Shimen National Forest Park, Guangzhou City, Guangdong Province, China were selected. Variations in the character of negative air ion concentration, air oxygen content, human comfort index and phytoncide relative content were analyzed. Principal component analysis and systematic clustering were used to construct forest comprehensive healthcare index and evaluation grade in order to assess the healthcare benefits of different forest types. In terms of negative air ion concentration, the subtropical evergreen broad-leaved forest was far ahead of the other forest types throughout the year, while the forestless control group was the worst. All stands reached the annual maximum in summer, followed by spring, autumn and winter. From the perspective of air oxygen content, summer &gt, spring &gt, autumn &gt, winter, among them, all forest stands clearly exceeded the normal atmospheric oxygen content (20.9%) in the first three quarters. Moreover, the air oxygen content of coniferous and broad-leaved mixed forest was the highest in five forest types, the forestless control group was the lowest. Judging from the human comfort index, in the whole year, all forest types, including the forestless group, were at the comfortable level and above. However, the five forest types still differed greatly in diverse seasons, among which Phyllostachys edulis forest and subtropical evergreen broad-leaved forest were superior to Liquidambar formosana forest, Cunninghamia lanceolata forest, coniferous and broad-leaved mixed forest in spring and summer, while it was in reverse in autumn and winter. In view of the phytoncide relative content, the subtropical evergreen broad-leaved forest was the highest, followed by the Cunninghamia lanceolata forest. The relative content of phytoncide was released more in summer, second, by spring, autumn and winter. Furthermore, establishing forest comprehensive healthcare index (FCHI = 0.1NAICi + 0.35AOCi + 0.27HCIi + 0.28PRCi), according to the FCHI value, it was divided into five rating levels. Overall, the comprehensive healthcare index of the five forest stands distinctly outperformed the forestless control group in all seasons. In addition, the five forest types were at level I in spring and summer. From the comprehensive data of the whole year, the comprehensive healthcare index of the coniferous and broad-leaved mixed forest was the best, followed by the subtropical evergreen broad-leaved forest. The forest environment has a favorable influence on the human body and mind, so it is suggested that citizens go to the forest environment regularly for healthcare and physical and mental washing. In terms of the forest healthcare benefits, the best seasons for forest therapy in Shimen National Forest Park are spring and summer, autumn is suitable as well. When planning and constructing the forest therapy bases in Shimen National Forest Park in the future, coniferous and broad-leaved mixed forests should be allocated more in the stand transformation to promote forest healthcare benefits. Protecting and developing the landscape resources of the subtropical evergreen broad-leaved forests should be paid close attention, as well as making rational use of their health activity space.

Transcription factors (TFs) act as key regulators in biological processes through controlling gene expression. Here, we conducted a systematic study for all human TFs on the expression, regulation, interaction, mutation, phenotype and cancer survival. We revealed that the average expression levels of TFs in normal tissues were lower than 50% expression of non-TFs, whereas TF expression was increased in cancers. TFs that are specifically expressed in an individual tissue or cancer may be potential marker genes. For instance, TGIF2LX/Y were preferentially expressed in testis and NEUROG1, PRDM14, SRY, ZNF705A and ZNF716 were specifically highly expressed in germ cell tumors. We found different distributions of target genes and TF co-regulations in different TF families. Some small TF families have huge protein interaction pairs, suggesting their central roles in transcriptional regulation. The bZIP family is a small family involving many signaling pathways. Survival analysis indicated that most TFs significantly affect survival of one or more cancers. Some survival-related TFs were also specifically highly expressed in the corresponding cancer types, which may be potential targets for cancer therapy. Finally, we identified 43 TFs whose mutations were closely correlated to survival, suggesting their cancer-driven roles. The systematic analysis of TFs provides useful clues for further investigation of TF regulatory mechanisms and the role of TFs in diseases.

Background: The prevalence of dementia in China, particularly in rural areas, is consistently increasing. Researchers have built upon the evidence that many dementia cases can be prevented, but most data came from high-income countries. Methods: A cross-sectional survey, named the China Multicentre Dementia Survey, was conducted. Face-to-face interviews, neuropsychological and clinical assessments were performed. Consensus dementia diagnoses were reached. Weighted population-attributable fractions (PAFs) were conducted for eight risk factors (six classical and two novels) in selected rural and urban areas, to identify potential dementia prevention targets. Findings: Overall, 17,589 respondents aged ≥ 65 years completed the survey between April 2018 and November 2020, 55.6% of whom were rural residents. The age and sex adjusted prevalence for all-cause dementia was 9.11% (95% CI 8.96–9.26), 5.19% (5.07–5.31), and 11.98% (11.8–12.15) in the whole, urban, and rural areas of China, respectively. And the overall weighted PAF of eight potentially modifiable risk factors was 53.72% (95% CI 52.73–54.71), 50.64% (49.4–51.89), and 56.54% (55.62–57.46), respectively. These eight risk factors’ profiles differed between rural and urban areas. Lower childhood education (PAF: 13.92%) and physical inactivity (16.99%) was the primary risk factor in rural and urban, respectively. Interpretation: The dementia prevalence has been increased in China over the past 5 years. The dementia prevention potential in China is greater than that reported worldwide. Resident-specific dementia prevention strategies should be developed. Funding: This work was financially supported by grants from the National Natural Science Foundation of China. Declaration of Interest: We declare no competing interests Ethical Approval: The protocol for this study was reviewed and approved by the Medical Ethics Committee at Wuhan University of Science and Technology (ID: 201845), and the Medical Ethics Committee at Tianjin Huanhu Hospital (ID: 2019-40). Please find the detailed ethical report from supplementary files. We confirm that the study was conducted in accordance with Helsinki Declaration as revised in 2013. We state that written informed consent was obtained from the participants of the study (and the relevant document(s) will be provided when requested by the journal). This study does not involving minor subjects/children/infants. We declare that personal details of patients in any part of the paper and in any supplementary materials (including illustrations) have been removed.

Immune checkpoint genes (ICGs) play critical roles in circumventing self-reactivity and represent a novel target to develop treatments for cancers. However, a comprehensive analysis for the expression profile of ICGs at a pan-cancer level and their correlation with patient response to immune checkpoint blockade (ICB) based therapy is still lacking. In this study, we defined three expression patterns of ICGs using a comprehensive survey of RNA-seq data of tumor and immune cells from the functional annotation of the mammalian genome (FANTOM5) project. The correlation between the expression patterns of ICGs and patients survival and response to ICB therapy was investigated. The expression patterns of ICGs were robust across cancers, and upregulation of ICGs was positively correlated with high lymphocyte infiltration and good prognosis. Furthermore, we built a model (ICGe) to predict the response of patients to ICB therapy using five features of ICG expression. A validation scenario of six independent datasets containing data of 261 patients with CTLA-4 and PD-1 blockade immunotherapies demonstrated that ICGe achieved area under the curves of 0.64–0.82 and showed a robust performance and outperformed other mRNA-based predictors. In conclusion, this work revealed expression patterns of ICGs and underlying correlations between ICGs and response to ICB, which helps to understand the mechanisms of ICGs in ICB signal pathways and other anticancer treatments.

Background Cancer genes tend to be highly mutated under positive selection. Better understanding the recurrently mutated genes (RMGs) in cancer is critical for explicating the mechanisms of tumorigenesis and providing vital clues for therapy. Although some studies have investigated functional impacts of RMGs in specific cancer types, a comprehensive analysis of RMGs and their mutational impacts across cancers is still needed. Methods We obtained data from The Cancer Genome Atlas (TCGA) and calculated mutation rate of each gene in 31 cancer types. Functional analysis was performed to identify the important signaling pathways and enriched protein types of RMGs. In order to evaluate functional impacts of RMGs, differential expression, survival, and pairwise mutation patterns analyses were performed. Results Totally, we identified 897 RMGs and 624 of them were specifically mutant in only a single cancer type. Functional analysis demonstrated that these RMGs were enriched in hydrolases, cytoskeletal protein, and pathways like MAPK, cell cycle, PI3K‐Akt, ECM receptor interaction, and energy metabolism. The differentially expressed genes potentially affected by the same common RMG showed a relatively low overlap across different cancer types. For the 19 Mucin (MUC) family genes, nine of them were RMGs and four of them (MUC17, MUC5B, MUC4, and MUC16) were common RMGs shared in 8 to 17 cancer types. The results showed that recurrent mutations in MUC genes were significantly associated with better survival prognosis. Only a small part of RMGs was differentially expressed due to their own mutations and most of them were downregulated. In addition, pairwise mutation pattern analysis revealed the high frequency of co‐occurred mutations among RMGs in STAD. Conclusion Through the functional analysis of RMGs, we found that six signaling pathways were disrupted in most cancer types and that energy metabolism was abnormal in tumors. The results also revealed a strong correlation between recurrently mutated genes from MUC family and human survival. In addition, gene expression and survival prognosis were associated with different mutation types of RMGs.

The pediatric T cell acute lymphoblastic leukemia (T-ALL) still remains a cancer with worst prognosis for high recurrence. Massive studies were conducted for the leukemia relapse based on diagnosis and relapse paired samples. However, the initially diagnostic samples may contain the relapse information and mechanism, which were rarely studied. In this study, we collected mRNA and microRNA (miRNA) data from initially diagnosed pediatric T-ALL samples with their relapse or remission status after treatment. Integrated differential co-expression and miRNA-transcription factor (TF)-gene regulatory network analyses were used to reveal the possible relapse mechanisms for pediatric T-ALL. We detected miR-1246/1248 and NOTCH2 served as key nodes in the relapse network, and they combined with TF WT1/SOX4/REL to form regulatory modules that influence the progress of T-ALL. A regulatory loop miR-429-MYCN-MFHAS1 was found potentially associated with the remission of T-ALL. Furthermore, we proved miR-1246/1248 combined with NOTCH2 could promote cell proliferation in the T-ALL cell line by experiments. Meanwhile, analysis based on the miRNA-drug relationships demonstrated that drugs 5-fluorouracil, ascorbate, and trastuzumab targeting miR-1246 could serve as potential supplements for the standard therapy. In conclusion, our findings revealed the potential molecular mechanisms of T-ALL relapse by the combination of co-expression and regulatory network, and they provide preliminary clues for precise treatment of T-ALL patients. Keywords: T-ALL, relapse, co-expression, network, drug

Background The cytogenetic aberrations were considered as markers for diagnosis and prognosis in acute myeloid leukemia (AML), while the expression and regulation under different cytogenetic groups remain to be fully elucidated. Methods In this paper, for favorable, poor, and cytogenetically normal groups of AML patients, we performed comprehensive bioinformatics analyses including identifying differentially expressed genes (DEGs) and microRNAs (miRNAs) among them, functional enrichment and regulatory networks. Results We found that DEGs were enriched in membrane‐related processes. Eleven genes and two miRNAs were significantly differentially expressed among these three AML groups. In survival analysis, membrane‐related genes and several miRNAs were significant on prognostic outcome. Notably, six HOXA and three HOXB genes were significantly in low expression and high methylation in AML with favorable cytogenetics. Meanwhile, the miRNA‐HOX gene co‐regulatory networks revealed that HOXA5 was a hub node and regulated an AML oncogene SPARC. Conclusion Our work may provide novel insights to the molecular characteristics and classification between AML with different cytogenetics., We integrated comprehensive bioinformatics analyses for genes between favorable, poor and cytogenetically normal (CN) groups of acute myeloid leukemia (AML) patients. We found that differentially expressed genes were enriched in membrane related processes. Eleven genes and two microRNAs were significantly differentially expressed among these 3 AML groups. Six HOXA and three HOXB genes was significantly in low expression and high methylation in AML with favorable cytogenetics.

Although there has been great progress in cancer treatment, cancer remains a serious health threat to humans because of the lack of biomarkers for diagnosis, especially for early-stage diagnosis. In this study, we comprehensively surveyed the specifically expressed genes (SEGs) using the SEGtool based on the big data of gene expression from the The Cancer Genome Atlas (TCGA) and the Genotype–Tissue Expression (GTEx) projects. In 15 solid tumors, we identified 233 cancer-specific SEGs (cSEGs), which were specifically expressed in only one cancer and showed great potential to be diagnostic biomarkers. Among them, three cSEGs (OGDH, MUDENG and ACO2) had a sample frequency >80% in kidney cancer, suggesting their high sensitivity. Furthermore, we identified 254 cSEGs as early-stage diagnostic biomarkers across 17 cancers. A two-gene combination strategy was applied to improve the sensitivity of diagnostic biomarkers, and hundreds of two-gene combinations were identified with high frequency. We also observed that 13 SEGs were targets of various drugs and nearly half of these drugs may be repurposed to treat cancers with SEGs as their targets. Several SEGs were regulated by specific transcription factors in the corresponding cancer, and 39 cSEGs were prognosis-related genes in 7 cancers. This work provides a survey of cancer biomarkers for diagnosis and early diagnosis and new insights to drug repurposing. These biomarkers may have great potential in cancer research and application.

Summary The availability of cancer genomic data makes it possible to analyze genes related to cancer. Cancer is usually the result of a set of genes and the signal of a single gene could be covered by background noise. Here, we present a web server named Gene Set Cancer Analysis (GSCALite) to analyze a set of genes in cancers with the following functional modules. (i) Differential expression in tumor versus normal, and the survival analysis; (ii) Genomic variations and their survival analysis; (iii) Gene expression associated cancer pathway activity; (iv) miRNA regulatory network for genes; (v) Drug sensitivity for genes; (vi) Normal tissue expression and eQTL for genes. GSCALite is a user-friendly web server for dynamic analysis and visualization of gene set in cancer and drug sensitivity correlation, which will be of broad utilities to cancer researchers. Availability and implementation GSCALite is available on http://bioinfo.life.hust.edu.cn/web/GSCALite/. Supplementary information Supplementary data are available at Bioinformatics online.

Coumarin-based “turn-off” fluorescent chemosensor, 3-acetoacetyl-7-diethylaminocoumarin ( 1 ), has been synthesized and structurally characterized by IR, 1 H NMR and X-ray crystal structure analysis. The fluorescence behaviors in the presence of various metal ions were investigated in aqueous media. 1 Exhibits highly selective and sensitive absorbance and fluorescence sensing ability for Cu 2+ over other metal ions. Addition of Cu 2+ to the aqueous solution of 1 gave rise to obvious absorbance change and fluorescence quenching. Other competing ions, such as Mg 2+ , Ba 2+ , Mn 2+ , Fe 3+ , Co 2+ , Ni 2+ , Zn 2+ , Pb 2+ , Cd 2+ , Hg 2+ , induced negligible absorbance and fluorescence changes under the same conditions. The job’s plot showed that the stoichiometry between 1 and Cu 2+ was estimated to be 1:1. The fluorescence intensity varied almost linearly vs. the concentration of Cu 2+ (1.0–7.0 μM), and the detection limit of Cu 2+ was estimated to be 1.81 nM, indicating that 1 can be used as “turn-off” fluorescent chemosensor to selectively detect Cu 2+ in aqueous solution.

Autophagy is an evolutionarily conserved response that can be activated in response to heavy metal. Thus, the present study investigated the effect of autophagy on neurotoxic damage caused by cadmium (Cd) in rat cerebral cortical neurons. The results indicated that the viability of cortical neurons treated with Cd was markedly decreased in a dose-and time-dependent manner. The present study provided evidence that cortical neurons treated with Cd underwent autophagy: The conversion of microtubule-associated protein 1A/1B-light chain 3 (LC3) to LC3-II, an increase in the punctate distribution of endogenous LC3-II and the presence of autophagosomes were identified. Combined treatment with Cd and chloroquine, an autophagy inhibitor, reduced the amount of autophagocytosis and cell activity, whereas rapamycin, an autophagy inducer, reduced Cd-mediated cytotoxicity. Furthermore, it was found that beclin-1 and class III phosphoinositide 3 kinase (PI3K) levels were increased, while levels of the anti-apoptotic protein B-cell lymphoma 2 (Bcl-2) were decreased after Cd treatment. LY294002, a specific inhibitor of PI3K, prevented the decline in Bcl-2 production and the increase in levels of beclin-1, class III PI3K and autophagy following Cd treatment. In conclusion, the results of the present study suggested that Cd can induce cytoprotective autophagy by activating the class III PI3K/beclin-1/Bcl-2 signaling pathway, and that the autophagy pathway can serve as a sensitive biomarker for nervous system injury after exposure to Cd.

C25H23N5O4, triclinic, P1̅ (no. 2), a = 8.157(2) Å, b = 9.262(2) Å, c = 15.465(4) Å, α = 87.887(4)°, β = 89.803(4)°, γ = 72.727(4)°, V = 1114.9(5) Å3, Z = 2, R gt (F) = 0.0755, wR ret (F 2 ) = 0.184, T = 298 K.

Objective To observe therapeutic effects of scalp acupuncture at close acupoints combined with rehabilitation training on balance functions of children with cerebral palsy (CP). Methods Sixty children with CP were randomly divided into a scalp acupuncture combined with rehabilitation training group (group SA+RT) and a rehabilitation training group (group RT) with 30 cases in each group. Conventional rehabilitation therapy and balance training were applied in group RT, and scalp acupuncture at close acupoints in the parietal region and sub-occipital region was added besides rehabilitation training in group SA+RT. Balance functions were evaluated by using Berg rating scale, and abilities of daily living were estimated by using rating scale for activities of daily living (ADL). Results After treatment, both Berg scores for balance and ADL scores were significantly improved in both groups (all P P Conclusion Combination of scalp acupuncture at close acupoints with rehabilitation training is superior to simple rehabilitation training in improving balance functions and activities of daily living in children with cerebral palsy.

Using density functional theory with generalized gradient approximation and hybrid functional, we studied the properties of energy, charge population, and vibration of CH2 and CH3 adsorbed on Cun (n = 1–6) clusters. The results show that the DFT calculation with the hybrid functional matches the experimental results better in both cases. The calculation results indicate that the adsorption of CH2 is stronger than that of CH3. During adsorption, the charges transfer from Cu to CH2 or CH3. The obtained vibrational frequencies for different modes of CH2 and CH3 adsorbed on Cun agree well with the experimental results for the adsorption on Cu(lll) surface.

To examine the role of Cd-induced reactive oxygen species (ROS) generation in the apoptosis of neuronal cells.Neuronal cells (primary rat cerebral cortical neurons and PC12 cells) were incubated with or without Cd post-pretreatment with rapamycin (Rap) or N-acetyl-L-cysteine (NAC). Cell viability was determined by MTT assay, apoptosis was examined using flow cytometry and fluorescence microscopy, and the activation of phosphoinositide 3'-kinase/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) and mitochondrial apoptotic pathways were measured by western blotting or immunofluorescence assays.Cd-induced activation of Akt/mTOR signaling, including Akt, mTOR, p70 S6 kinase (p70 S6K), and eukaryotic initiation factor 4E binding protein 1 (4E-BP1). Rap, an mTOR inhibitor and NAC, a ROS scavenger, blocked Cd-induced activation of Akt/mTOR signaling and apoptosis of neuronal cells. Furthermore, NAC blocked the decrease of B-cell lymphoma 2/Bcl-2 associated X protein (Bcl-2/Bax) ratio, release of cytochrome c, cleavage of caspase-3 and poly(ADP-ribose) polymerase (PARP), and nuclear translocation of apoptosis-inducing factor (AIF) and endonuclease G (Endo G).Cd-induced ROS generation activates Akt/mTOR and mitochondrial pathways, leading to apoptosis of neuronal cells. Our findings suggest that mTOR inhibitors or antioxidants have potential for preventing Cd-induced neurodegenerative diseases.

To understand the blood lead level and its influencing factors of workers in one lead acid storage cell enterprise in Jiangsu Province.An occupational health field investigation was done to this storage cell enterprise at the end of June 2011 to measure the air lead fume (dust) concentration of workplaces. Health-care information of 1364 person-times from 2009 - 2011 was collected, including blood lead level, general state of health, life and health habit. One way ANOVA and ordinal multi-categorical logistic stepwise regression were used to analysis the influencing factors of blood lead level.The lead fume concentration range was 0.008-0.354 mg/m(3) among 12 measuring points, which 7 places were unqualified, while the concentration range of lead dust was 0.023 - 2.432 mg/m(3), 24 out of 27 measuring places were unqualified, both the qualified rate were low. The blood lead concentration of objects was (259.54 ± 106.62) µg/L, among which 96 people (7.04%) who ≥ 400 µg/L should be identified as suspected "observation object", blood lead concentration ≥ 600 µg/L was not found. The blood lead concentration of male (279.76 ± 114.93 µg/L) was significantly higher than female (242.44 ± 95.86) µg/L (t = 6.441, P0.01). The proportion of ≥ 400 µg/L in male (11.04%, 69/625) was significantly higher than female (3.65%, 27/739) (χ(2) = 28.237, P0.01). The blood lead concentration of workers who exposed to lead fume or dust (265.93 ± 103.70) µg/L was significantly higher than those of not exposed to lead (205.30 ± 115.62) µg/L (t = -6.037, P0.01), the blood lead concentration of workers who exposed to lead dust was (267.38 ± 98.02) µg/L significantly higher than those of exposed to lead fume (260.81 ± 121.80) µg/L (t = -2.408, P0.05). The proportion of ≥ 400 µg/L in workers who exposed to lead fume (dust) (7.60%, 93/1223) was significantly higher than those of not exposed to lead (2.13%, 3/141) (χ(2) = 4.538, P0.05). Ordinal multi-categorical logistic stepwise regression found that the lead fume concentration ≥ 0.03 mg/m(3), lead dust concentration ≥ 0.05 mg/m(3) (OR = 1.59, 95%CI: 1.06 - 2.39), length of service ≥ 3 years (OR = 1.82, 95%CI: 1.12 - 2.98), smoking (OR = 2.06, 95%CI: 1.27 - 3.37) can increase the level of blood lead concentration.Lead dust concentration of the enterprise exceeded the standard. Workers exposed to lead fume (dust) have more occupational health hazard of lead, of whom the blood lead concentration was high. Higher lead fume (dust) concentration in workplace, longer length of service, smoking were risk factors of high blood lead concentration.